Endocrine Abstracts

Introduction: The development of molecular biology and cancer immunology has brought drastic changes in anticancer in recent years. Recently, tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICPIs) have emerged as new classes of anticancer therapies. Although generally considered less toxic than cytotoxic chemotherapy, these new drugs can cause significant side effects including thyroid dysfunction. We report the case of thyroiditis induced by Pembrolizumab (ICPIs) plus Lenvatinib (TKI) in patient with metastatic renal cell carcinoma.

Observation: A 72 years old male patient with a history of type 2 diabetes mellitus, arterial hypertension, was diagnosed with metastatic renal cell carcinoma and treated by pembrolizumab plus Lenvatinib. Two months after the start of this association, he was presented to the emergency department with a history of vertigo and tachycardia. Thyroid function tests revealed transient hyperthyroidism with negative TRAK, TPO and TG antibodies. The cervical ultrasound had showed a small thyroid with hypoechoic parenchyma, low vascularity consistent with thyroiditis. He was put on 40 mg of Carbimazole per day and 40 mg of Propanolol twice per day. His thyroid function was subsequently monitored until he was found to have overt hypothyroidism and put on under 200 µg of levothyroxine per day.

Discussion & Conclusion: In patients treated with TKIs or ICPIs, the thyroid toxicities are common and pauci-symptomatic at the beginning of their evolution but can lead to prolonged hypothyroidism that should not be ignored. The cumulative clinical experience of recent years and the basic studies have led to a better understanding of the mechanisms of thyroid dysfunction. Schematically, the iatrogenic thyroiditis of TKIs is linked to vascular damage related to their selectivity to block diverse vascular growth factor signaling pathways which may led to a rapid reduction in thyroid vascular flow and as a result the occurrence of ischemic thyroiditis. In the other hand, the iatrogenic thyroiditis of ICPIs is based on an inflammatory mechanism by autoimmune reaction that in many cases is accompanied by hormonal deficiency in the long term. As the use of these antibodies becomes more prelevent, more investigations and research are needed to identify risk factors for these side effects and possibly tailor the treatment of patients accordingly. Finally, thyroid function tests including TSH, FT4 and TPO antibodies screening should be a part of baseline of laboratory testing of all patient undergoing treatment with these drugs.